全文获取类型
收费全文 | 18833篇 |
免费 | 1695篇 |
国内免费 | 1432篇 |
专业分类
21960篇 |
出版年
2023年 | 242篇 |
2022年 | 531篇 |
2021年 | 894篇 |
2020年 | 604篇 |
2019年 | 687篇 |
2018年 | 726篇 |
2017年 | 538篇 |
2016年 | 699篇 |
2015年 | 1148篇 |
2014年 | 1266篇 |
2013年 | 1364篇 |
2012年 | 1564篇 |
2011年 | 1498篇 |
2010年 | 982篇 |
2009年 | 833篇 |
2008年 | 906篇 |
2007年 | 875篇 |
2006年 | 771篇 |
2005年 | 656篇 |
2004年 | 617篇 |
2003年 | 543篇 |
2002年 | 515篇 |
2001年 | 392篇 |
2000年 | 390篇 |
1999年 | 359篇 |
1998年 | 169篇 |
1997年 | 161篇 |
1996年 | 158篇 |
1995年 | 119篇 |
1994年 | 146篇 |
1993年 | 90篇 |
1992年 | 155篇 |
1991年 | 147篇 |
1990年 | 122篇 |
1989年 | 98篇 |
1988年 | 82篇 |
1987年 | 96篇 |
1986年 | 83篇 |
1985年 | 92篇 |
1984年 | 48篇 |
1983年 | 48篇 |
1982年 | 48篇 |
1981年 | 36篇 |
1980年 | 37篇 |
1979年 | 52篇 |
1978年 | 41篇 |
1977年 | 45篇 |
1976年 | 33篇 |
1975年 | 35篇 |
1974年 | 44篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
2,4-D和6-BA对向日葵下胚轴愈伤组织生长及钙调蛋白的影响 总被引:2,自引:0,他引:2
自 Anderson和 Cormier(1979)从植物中分离提取钙调蛋白(简称 CaM)后,对它的结构功能进行了广泛的研究,发现 CaM在光合作用(Barr等 1980)、酶的激活(Matsumoto等 1983)、蛋白磷酸化(Gideon等1982)等方面均起着重要作用。还证明CaM与生长素、细胞分裂素以及α-淀粉酶的分泌等有密切关系(Elliott 1983,Raghothama等1983;Saunders等1982)Elliott认为植物激素的促 相似文献
972.
Chenyang Ji Chang Yu Jianqiang Zhu Yafei Cheng Tian Tian Bingqi Zhou Jinping Gu Jun Fan Meirong Zhao 《Chirality》2020,32(8):1107-1118
Cypermethrin (CP) is widely used for controlling agricultural and indoor vermin. Previous studies have reported the stereoselective difference of CP in biological activities. However, little is known about their potential mechanisms between metabolic phenotypes and endocrine-disrupting effects. Herein, nuclear magnetic resonance (NMR)-based metabolomics combining metabolite identification and pathway analysis were applied to evaluate the stereoselective metabolic cdisorders induced by CP isomers in human adrenocortical carcinoma cells (H295R) culture medium. Then, gene expression levels related to disturbed metabolic pathways were assessed to verify according to metabolic phenotypes. Metabolomics profiles showed that [(S)-cyano(3-phenoxyphenyl)methyl](1R,3R)-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate [(1R,3R,αS)-CP] induced the most significant changes in metabolic phenotypes than did the other stereoisomers. There are 10 differential metabolites (isoleucine, valine, leucine, ethanol, alanine, acetate, aspartate, arginine, lactate, and glucose) as well as two significantly disturbed pathways, including “pyruvate metabolism” and “alanine, aspartate, and glutamate metabolism,” that were confirmed in H295R cells culture medium of (1R,3R,αS)-CP compared with other stereoisomers. Polymerase chain reaction (PCR) array also confirmed the results of metabolomics. Our results can help to understand the potential mechanisms between the isomer selectivity in metabolic phenotypes and endocrine-disrupting effects. Data provided here not only lend authenticity to the cautions issued by the scientists and researchers but also offer a solution for the balance between environment and political regulations. 相似文献
973.
Xin Liao Wei Zhan Jiandong Zhang Zhongsheng Cheng Lianghe Li Tian Tian Lei Yu Rui Li 《Journal of cellular biochemistry》2020,121(10):4295-4309
Colorectal cancer is one of the most common and leading malignancies globally. Long noncoding RNAs (lncRNAs) function as potentially critical regulator in colorectal cancer. LINC01234, a novel lncRNA in tumor biology, regulates the progression of various tumors. However, the tumorigenic mechanism of LINC01234 in colorectal cancer is still unclear. This study was performed with the aim to prospectively investigate clinical significance, effect, and mechanism of lncRNA LINC01234 in colorectal cancer. First, we found that LINC01234, localized in the cytoplasm, was increased in both colorectal cancer cell lines and tissues. Subsequent functional assays suggested LINC01234 knockdown suppressed cell proliferation, migration, and invasion of colorectal cancer cells, while blocked cell cycle and induced cell apoptosis. Moreover, we identified that miR-1284 was target of LINC01234, we further demonstrated a negative correlation with LINC01234 in colorectal cancer tissues and cells. Furthermore, miR-1284 targeted and suppressed tumor necrosis factor receptor–associated factor 6 (TRAF6). Loss-of-function assay revealed that LINC01234 silencing suppressed colorectal cancer progression through inhibition of miR-1284. In vivo subcutaneous xenotransplanted tumor model indicated LINC01234 knockdown inhibited in vivo tumorigenic ability of colorectal cancer via downregulation of TRAF6. Collectively, this study clarified the biological significance of LINC01234/miR-1284/TRAF6 axis in colorectal cancer progression, providing insights into LINC01234 as novel potential therapeutic target for colorectal cancer therapeutic from bench to clinic. 相似文献
974.
Chongchong Wang Li Cheng Shasha Song Shan Wu Guoping Sun 《Journal of cellular physiology》2020,235(11):8224-8235
Esophageal squamous cell carcinoma (ESCC) is the predominant esophageal cancer type in China. The aberrant activation of glioma-associated oncogene homolog1 (Gli1), a key factor in Hedgehog (Hh) signaling pathway, has been found in esophageal carcinoma. Moreover, Yes-associated protein 1 (YAP1), the major mediator of Hippo signaling pathway, has been linked to esophageal carcinoma progression. However, the precise roles and the underlying mechanism of both Gli1 and YAP1 in ESCC are unclear. Here, we found that Gli1 and YAP1 are overexpressed in ESCC and are associated with poor prognosis. In addition, we confirmed that knockdown of Gli1 or YAP1 suppresses ESCC cell growth, migration, and invasion in ESCC TE1 and EC109 cells. Significantly, Gli1 interacts with YAP1 in ESCC cells. Both Gli1 and YAP1 proteins are closely correlated with each other in human ESCC samples. Mechanistically, Gli1 upregulates YAP1 in a LATS1-independent manner. Conversely, YAP1 induces Gli1 by regulating phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Most importantly, we demonstrated that the interaction between Gli1 and YAP1 promotes ESCC tumor growth in vitro and in vivo. Our findings established a novel signaling mechanism by which the interaction between Gli1 and YAP1 promotes ESCC cell growth. This signaling regulation of the tumorigenesis provides a new therapeutic strategy for highly lethal ESCC. 相似文献
975.
976.
Hao Fu Lin Cheng Ri Sa Yuchen Jin Libo Chen 《Journal of cellular and molecular medicine》2020,24(6):3336-3345
Clinical efficacy of differentiation therapy with mitogen-activated protein kinase inhibitors (MAPKi) for lethal radioiodine-refractory papillary thyroid cancer (RR-PTC) urgently needs to be improved and the aberrant trimethylation of histone H3 lysine 27 (H3K27) plays a vital role in BRAFV600E-MAPK-induced cancer dedifferentiation and drug resistance. Therefore, dual inhibition of MAPK and histone methyltransferase (EZH2) may produce more favourable treatment effects. In this study, BRAFV600E-mutant (BCPAP and K1) and BRAF-wild-type (TPC-1) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine-metabolizing genes, radioiodine uptake, and toxicity were tested. We found that tazemetostat alone slightly increased iodine-metabolizing gene expression and promoted radioiodine uptake and toxicity, irrespective of the BRAF status. However, MAPKi induced these effects preferentially in BRAFV600E mutant cells, which was robustly strengthened by tazemetostat incorporation. Mechanically, MAPKi-induced decrease of trimethylation of H3K27 was evidently intensified by tazemetostat in BRAFV600E-mutant cells. In conclusion, tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy. 相似文献
977.
Liyu Chen Haiyang Nan Lingping Kong Lin Yue Hui Yang Qingsong Zhao Chao Fang Haiyang Li Qun Cheng Sijia Lu Fanjiang Kong Baohui Liu Lidong Dong 《植物学报(英文版)》2020,62(12):1868-1879
Flowering time and plant height are key agronomic traits that directly affect soybean (Glycine max) yield. APETALA1 (AP1) functions as a class A gene in the ABCE model for floral organ development, helping to specify carpel, stamen, petal, and sepal identities. There are four AP1 homologs in soybean, all of which are mainly expressed in the shoot apex. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR) – CRISPR‐associated protein 9 technology to generate a homozygous quadruple mutant, gmap1, with loss‐of‐function mutations in all four GmAP1 genes. Under short‐day (SD) conditions, the gmap1 quadruple mutant exhibited delayed flowering, changes in flower morphology, and increased node number and internode length, resulting in plants that were taller than the wild type. Conversely, overexpression of GmAP1a resulted in early flowering and reduced plant height compared to the wild type under SD conditions. The gmap1 mutant and the overexpression lines also exhibited altered expression of several genes related to flowering and gibberellic acid metabolism, thereby providing insight into the role of GmAP1 in the regulatory networks controlling flowering time and plant height in soybean. Increased node number is the trait with the most promise for enhancing soybean pod number and grain yield. Therefore, the mutant alleles of the four AP1 homologs described here will be invaluable for molecular breeding of improved soybean yield. 相似文献
978.
Xue-Jun Cheng Fu-Lai Guan Qian Li Gong Dai Hai-Feng Li Xue-Kun Li 《World journal of stem cells》2020,12(11):1354-1365
BACKGROUNDAs the third most abundant element, aluminum is widespread in the environment. Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIMTo study the effects of aluminum on epigenetic modification in neural stem cells and neurons. METHODSNeural stem cells were isolated from the forebrain of adult mice. Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice. AlCl3 at 100 and 200 μmol/L was applied to stem cells and neurons. RESULTSAluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells. Aluminum application also significantly inhibited the dendritic development of hippocampal neurons. Mechanistically, aluminum exposure significantly affected the levels of DNA 5-hydroxy-methylcytosine, 5-methylcytosine, and N6-methyladenine in stem cells and neurons. CONCLUSIONOur findings indicate that aluminum may regulate neuronal development by modulating DNA modifications. 相似文献
979.
Cheng Peng Qing Wang Herong Shi Jiaxing Chen Shuisheng Li Huihong Zhao Haoran Lin Jianchun Yang Yong Zhang 《Journal of fish biology》2020,97(3):785-793
Sexual patterns of teleosts are extremely diverse and include both gonochorism and hermaphroditism. As a protogynous hermaphroditic fish, all orange-spotted groupers (Epinephelus coioides) develop directly into females, and some individuals change sex to become functional males later in life. This study investigated gonadal restructuring, shifts in sex hormone levels and gene profiles of cultured mature female groupers during the first (main) breeding season of 2019 in Huizhou, China (22° 42′ 02.6″ N, 114° 32′ 10.1″ E). Analysis of gonadal restructuring revealed that females with pre-vitellogenic ovaries underwent vitellogenesis, spawning and regression and then returned to the pre-vitellogenic stage in the late breeding season, at which point some changed sex to become males via the intersex gonad stage. A significant decrease in the level of serum 17β-estradiol (E2) was observed during ovary regression but not during sex change, whereas serum 11-ketotestosterone (11-KT) concentrations increased significantly during sex change with the highest concentration in newly developed males. Consistent with serum hormone changes, a significant decrease in cyp19a1a expression was observed during ovary regression but not during sex change, whereas the expression of cyp11c1 and hsd11b2 increased significantly during sex change. Interestingly, hsd11b2 but not cyp11c1 was significantly upregulated from the pre-vitellogenic ovary stage to the early intersex gonad stage. These results suggest that a decrease in serum E2 concentration and downregulation of cyp19a1a expression are not necessary to trigger the female-to-male transformation, whereas increased 11-KT concentration and upregulation of hsd11b2 expression may be key events for the initiation of sex change in the orange-spotted grouper. 相似文献
980.